Allopurinol vs Alternatives: Full Gout Medication Comparison (2025)

TL;DR

• Allopurinol works for most gout patients but needs dose adjustment in kidney disease.
• Febuxostat is a non‑purine xanthine oxidase inhibitor, useful when allopurinol isn’t tolerated.
• Probenecid increases uric acid excretion; best for patients with good kidney function.
• Pegloticase is an IV enzyme for refractory gout; high cost and infusion reactions limit use.
• Lesinurad adds uricosuric power to xanthine oxidase inhibitors but raises kidney‑stone risk.

Gout flares are painful, but the right medication can keep uric acid under control for the long haul. If you’ve been prescribed allopurinol alternatives, you’re probably wondering how they stack up. This guide walks through the chemistry, dosing, side‑effects, and real‑world considerations for the most common gout drugs, so you can match the treatment to your health profile.

What is gout and why do we need uric‑lowering drugs?

Gout is an inflammatory arthritis triggered by high levels of uric acid in the blood (hyperuricemia). When urate crystals deposit in joints, they spark sudden, throbbing pain. Keeping serum urate below 6mg/dL (or Hyperuricemia a condition where blood uric acid exceeds normal limits, often above 7mg/dL) reduces flare frequency and prevents joint damage.

Two main drug classes lower uric acid:

• Xanthine oxidase inhibitors medications that block the enzyme that produces uric acid (e.g., Allopurinol, Febuxostat).
• Uricosuric agents drugs that increase kidney excretion of uric acid (e.g., Probenecid, Lesinurad).

Choosing the right class depends on kidney health, other medicines, and how your body reacts.

Allopurinol - the classic workhorse

Allopurinol a purine‑type xanthine oxidase inhibitor approved for gout and hyperuricemia has been on the market since the 1960s. It reduces uric‑acid production by blocking the enzyme xanthine oxidase.

Typical dose: start 100mg daily, increase by 100mg every 2-4weeks up to 300mg (or 400mg in select cases) based on serum urate and renal function.

Key advantages:

• Low cost (generic price ~£0.10 per tablet in the UK).
• Well‑studied safety profile with decades of data.
• Effective for most patients when titrated properly.

Common side effects:

• Skin rash (rare but can progress to Stevens‑Johnson syndrome).
• Transient liver enzyme rise.
• Gout flare during dose escalation (prevent with prophylactic colchicine or NSAIDs).

Allopurinol is cleared by the kidneys, so Renal impairment reduced kidney function measured by eGFR, impacting drug elimination requires dose reduction. In patients with eGFR<30mL/min, a starting dose of 50mg daily is typical.

Febuxostat - the non‑purine alternative

Febuxostat a non‑purine selective xanthine oxidase inhibitor approved for gout and hyperuricemia was introduced in the early 2000s. It works similarly to Allopurinol but does not need renal dose adjustment.

Typical dose: 40mg once daily; increase to 80mg if target urate not reached after 2weeks.

Advantages:

• Effective even in moderate‑to‑severe renal dysfunction (eGFR<30mL/min).
• Lower incidence of rash compared with high‑dose Allopurinol.
• Predictable pharmacokinetics - less titration required.

Safety notes:

• FDA boxed warning for increased cardiovascular mortality (observed in high‑risk patients).
• Possible liver enzyme elevation - monitor ALT/AST.
• May cause nausea or mild allergic rash.

Cost is higher than Allopurinol (brand price ~£0.50‑£0.80 per tablet), but many UK NHS formularies list it as a second‑line option when Allopurinol cannot be used.

Probenecid - the classic uricosuric

Probenecid a uricosuric agent that blocks renal tubular reabsorption of uric acid, increasing its excretion has been used for decades, especially in patients who cannot tolerate xanthine oxidase inhibitors.

Typical dose: 250mg twice daily; may increase to 1g twice daily.

When it shines:

• Patients with normal kidney function (eGFR>60mL/min).
• Those who already have low serum urate but need a boost.

Limitations:

• Ineffective in renal impairment because it relies on tubular function.
• Increases risk of calcium‑oxalate kidney stones.
• Drug interactions with penicillins, NSAIDs, and antivirals.

Side effects include GI upset, rash, and rarely, hemolysis in G6PD‑deficient patients.

Pegloticase - the IV enzyme for refractory gout

Pegloticase a recombinant uricase enzyme given intravenously to metabolize uric acid into allantoin is reserved for chronic gout that fails to respond to oral agents.

Dosing: 8mg IV infusion every 2 weeks.

Pros:

• Rapid urate reduction (often <6mg/dL within days).
• Effective in patients with severe renal disease.

Cons:

• High price (≈£30,000 per year in the UK).
• Infusion reactions in up to 30% of patients - requires pre‑medication and monitoring.
• Development of anti‑drug antibodies reduces efficacy over time.

Because of cost and safety concerns, Pegloticase is used only after trial of xanthine oxidase inhibitors and uricosurics.

Lesinurad - the uricosuric add‑on

Lesinurad a selective inhibitor of the uric acid transporter URAT1, used in combination with a xanthine oxidase inhibitor was approved in 2015.

Typical dose: 200mg once daily together with Allopurinol or Febuxostat.

Why add it?

• Boosts uric‑acid excretion when XO inhibition alone isn’t enough.
• Helps patients on maximum tolerated XO inhibitor dose reach target urate.

Cautions:

• Increases risk of nephrolithiasis - ensure adequate hydration.
• Contraindicated in eGFR<30mL/min.
• May cause mild hepatic enzyme rise.

Cost is moderate (£0.30-£0.45 per tablet) and most UK NHS trusts cover it when combined with standard therapy.

Side‑by‑side comparison

How to pick the right drug for you

Consider these factors before settling on a regimen:

1. Kidney function: If eGFR<30mL/min, Febuxostat or Pegloticase are safer bets than Allopurinol or Probenecid.
2. Cardiovascular history: Patients with recent heart disease should discuss Febuxostat’s risk versus Allopurinol’s lower cardiovascular profile.
3. Previous drug reactions: A history of rash with Allopurinol pushes you toward Febuxostat or a uricosuric if kidneys are healthy.
4. Cost & insurance coverage: Generic Allopurinol remains the most affordable; Pegloticase may require special approval.
5. Need for rapid control: Pegloticase achieves fast urate reduction, useful before surgery or in severe tophi cases.

Always combine the chosen drug with lifestyle changes - low‑purine diet, weight loss, limiting alcohol, and staying hydrated. For most people, a low dose of colchicine during the first 3 months of therapy helps prevent flares caused by shifting uric‑acid levels.

Frequently Asked Questions

Choosing a gout medicine isn’t a one‑size‑fits‑all decision. By weighing kidney health, cardiovascular risk, cost, and how fast you need urate control, you can land on the regimen that keeps you pain‑free and moving.